A Clinical Study Of Anti-N-methyl-D-aspartate Receptor Encephalitis Secondary To Japanese Encephalitis

PART 1 THE RETROSPECTIVE STUDY ON BIPHASIC JAPANESE ENCEPHALITIS AND THE TEST FOR ANTI-NMDAR IGGObjectives:To investigate if the biphasic Japanese encephalitis is anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis secondary to Japanese encephalitis.Methods:Retrospectively reviewed the clinical data of three biphasic Japanese encephalitis patients.Cell based assay(CBA)was conducted to test for the presence of anti-NMDAR IgG in their CSF and serum.Results:The three patients presented with the clinical manifestations of anti-NMDAR encephalitis,and the anti-NMDAR IgG was positive in their CSF,confirming the diagnosis of anti-NMDAR encephalitis.Conclusions:Patients with Japanese encephalitis may develop relapsing anti-NMDAR encephalitis after a partial recovery,giving rise to a biphasic pattern for the disease.PART 2 THE PROSPECTIVE CLINICAL STUDY OF ANTI-NMDAR-IGG IN JAPANESE ENCEPHALITIS PATIENTSObjectives:To explore following questions:1.If the anti-NMDAR IgG exist in all Japanese encephalitis patients?2.If it exists,when does it appear?In acute phase or in convalescence?3.If anti-NMDAR IgG was generally induced by Japanese encephalitis(especially Japanese encephalitis with monophasic pattern)?4.Are there risk factors for anti-NMDAR encephalitis secondary to Japanese encephalitis?Methods:65 patients with Japanese encephalitis met with the inclusion criteria in 2017.Test for anti-NMDAR IgG in serum and CSF in acute phase was conducted.After following up,test for anti-NMDAR-IgG in serum in convalescence was conducted again.If patients had a relapse after a partial recovery showing biphasic pattern for the disease,they would be admitted to hospital again and had reexaminations such as CSF test and MRI,as well as test for anti-NMDAR IgG in serum and CSF.Immunotherapy was also conducted to them.The clinical data was analyzed to seek risk factors for anti-NMDAR encephalitis secondary to Japanese encephalitis.Results:1.Samples of serum and CSF in acute phase from all of the 65 patients were negative for anti-NMDAR IgG;2.63 patients were successfully followed up.Five patients had relapse after a partial recovery,giving rise to a biphasic pattern for the disease.Three out of the five patients had positive result of NMDAR-IgG test in CSF and were diagnosed as anti-NMDAR encephalitis;the other two patients had negative result.3.58 patients had monophasic Japanese encephalitis and the results of NMDAR-IgG test in serums in convalescence were all negative;4.Since three patients with anti-NMDAR encephalitis secondary to Japanese encephalitis is quite a small sample,it’s unable to do statistic analysis of the risk factors for anti-NMDAR encephalitis secondary to Japanese encephalitis.Conclusions:1.Samples of serum and CSF in acute phase from all patients were negative for anti-NMDAR IgG,illustrating that the anti-NMDAR IgG were indeed induced by encephalitis B virus infection of central nervous system;2.Anti-NMDAR IgG was not generally induced by Japanese encephalitis.For patients had Japanese encephalitis with monophasic pattern,the anti-NMDAR-IgG were negative in serum in convalescence;3.Not all patients with biphasic Japanese encephalitis had positive result of anti-NMDAR IgG test in CSF,which suggesting that other antibodies of autoimmune encephalitis may be induced by encephalitis B virus infection of central nervous system.PART 3 SUMMARY OF CLINICAL DATA OF PATIENTS WITH BIPHASIC JAPANESE ENCEPHALITIS AND NEGATIVE RESULTS OF ANTI-NMDAR IGG TEST AND THE TEST OF OTHER ANTIBODIES OF AUTOIMMUNE ENCEPHALITISObjectives:To investigate if other antibodies of autoimmune encephalitis existed in patients with biphasic Japanese encephalitis and negative results of anti-NMDAR IgG test and to summarize the clinical characteristics of these patients.Methods:Detect commonly known antibodies of autoimmune encephalitis(Anti-AMPA receptor 1-IgG,anti-AMPA receptor 2-IgG,anti-LGI1-IgG,anti-CASPR2-IgG,anti-GABA-B receptor-IgG)by cell based assay(CBA)in serum and CSF of the two patients with biphasic Japanese encephalitis and negative results of anti-NMDAR IgG test in the second part of this dissertation.If the result was also negative,further detection would be done for other unknown antibodies of autoimmune encephalitis by tissue based assay(TBA).The detailed clinical data of the two patients were collected.Results:The test of commonly known antibodies of autoimmune encephalitis in serum and CSF of the two patients were all negative,but the TBA revealed unknown antibodies which reacted with rat hippocampal tissue.According to the clinical manifestations,MRI findings and TBA results,the diagnosis of autoimmune encephalitis was confirmed for the two patients.Conclusions:Except for anti-NMDAR IgG,other unknown antibodies of autoimmune encephalitis could also be induced by encephalitis B virus infection of central nervous system.